Development and Testing of Gene-editing for Epidermolytic Ichthyosis
Dr Joanna Jacków-Malinowska and Professor John McGrath
Project Duration: 3 year PhD; Project Start date: 1st February 2025
Total Project Cost: £129,000
EI Cure Project Award: £29,000; Project Collaborator: Rosetrees Trust
Development and testing of gene editing for epidermolytic ichthyosis
Summary of the Project
The primary objective is to explore the use of gene-editing tools, including base-editing, prime-editing, and PASTE technology to establish whether it is possible to move from a personalised treatment for a specific phenotype to a ‘One size fits all’ approach for a genotype. The secondary objective is to explore if these gene editing tools can be transfected into the skin with a Lipid-nanoparticle vector, for the eventual development of a gene-cream for topical treatment delivery.
Genetic variants included in the Project
Epidermolytic Ichthyosis Pathogenic Variants on KRT1 and KRT10 (Results will also be applicable to KRT2)
Main outcomes anticipated from the Project
This project encompasses new gene editing technology to try to develop innovative therapies for EI. To date, there have been no reports of gene editing (base editing or PASTE) for epithelial keratins or EI. Thus, this project will develop a new application for gene editing in skin disease and will create original cell culture models to assess the impact of gene editing correction on skin function (repairing the skin thickening and scaling), as well as exploring the potential to develop a topical gene cream for future clinical testing in EI. Ultimately, this project is about bringing the prospects of correcting the abnormal genes in EI closer to the time when people with EI can engage in clinical trials of "Gene Therapy".